RESUMEN
Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies. By examining how metal ions modulate the innate and adaptive immune systems, as well as host-microbiota interactions, we discuss strategies for the development of such metalloimmunotherapies for the treatment of cancer and other immune-related diseases.
Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Animales , Metales , Inmunidad Innata , Inmunidad AdaptativaRESUMEN
The high prevalence and rising incidence of autoimmune diseases have become a prominent public health issue. Autoimmune disorders result from the immune system erroneously attacking the body's own healthy cells and tissues, causing persistent inflammation, tissue injury, and impaired organ function. Existing treatments primarily rely on broad immunosuppression, leaving patients vulnerable to infections and necessitating lifelong treatments. To address these unmet needs, an emerging frontier of vaccine development aims to restore immune equilibrium by inducing immune tolerance to autoantigens, offering a potential avenue for a cure rather than mere symptom management. We discuss this burgeoning field of vaccine development against inflammation and autoimmune diseases, with a focus on common autoimmune disorders, including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Vaccine-based strategies provide a new pathway for the future of autoimmune disease therapeutics, heralding a new era in the battle against inflammation and autoimmunity.
Asunto(s)
Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Vacunas , Humanos , Lupus Eritematoso Sistémico/complicaciones , Autoinmunidad , Tolerancia Inmunológica , Inflamación , Vacunas/uso terapéuticoRESUMEN
Inflammatory bowel disease (IBD) is characterized by the chronic inflammation of the gastrointestinal tract and impacts almost 7 million people across the globe. Current therapeutics are effective in treating the symptoms, but they often do not address the root cause or selectively target areas of inflammation. Notably, self-assembled nanoparticles show great promise as drug delivery systems for the treatment of IBD. Nanoparticles can be designed to survive the harsh gastric conditions and reach inflamed areas of the gastrointestinal tract. Oral drug delivery with nanoparticles can localize drugs to the impacted inflamed region using active and/or passive targeting and promote a high rate of drug dispersion in local tissues, thus reducing potential off-target toxicities. Since a dysregulated gut microbiome is implicated in the development and progression of IBD, it is also important to develop nanoparticles and biomaterials that can restore symbiotic microbes while reducing the proliferation of harmful microbes. In this review, we highlight recent advances in self-assembled nanosystems designed for addressing inflammation and dysregulated gut microbiomes as potential treatments for IBD. Nanoparticles have a promising future in improving the delivery of current therapeutics, increasing patient compliance by providing an oral method of medication, and reducing side effects. However, remaining challenges include scale-up synthesis of nanoparticles, potential side effects, and financial obstacles of clinical trials. It would be in the patients' best interest to continue research on nanoparticles in the pursuit of more effective therapeutics for the treatment of IBD.
Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Inflamación/tratamiento farmacológico , Nanotecnología , Preparaciones Farmacéuticas , Enfermedad CrónicaRESUMEN
The global transcriptional response of Escherichia coli to styrene and potential influence of exposure source was determined by performing RNA sequencing (RNA-seq) analysis on both styrene-producing and styrene-exposed cells. In both cases, styrene exposure appears to cause both cell envelope and DNA damage, to which cells respond by down-regulating key genes/pathways involved in DNA replication, protein production, and cell wall biogenesis. Among the most significantly up-regulated genes were those involved with phage shock protein response (e.g. pspABCDE/G), general stress regulators (e.g. marA, rpoH), and membrane-altering genes (notably, bhsA, ompR, ldtC), whereas efflux transporters were, surprisingly, unaffected. Subsequent studies with styrene addition demonstrate how strains lacking ompR [involved in controlling outer membrane (OM) composition/osmoregulation] or any of tolQ, tolA, or tolR (involved in OM constriction) each displayed over 40% reduced growth relative to wild-type. Conversely, despite reducing basal fitness, overexpression of plsX (involved in phospholipid biosynthesis) led to 70% greater growth when styrene exposed. These collective differences point to the likely importance of OM properties in controlling native styrene tolerance. Overall, the collective behaviours suggest that, regardless of source, prolonged exposure to inhibitory styrene levels causes cells to shift from'growth mode' to 'survival mode', redistributing cellular resources to fuel native tolerance mechanisms.